Ampoules prefilled with various components are manufactured for diverse purposes. The present invention is mainly concerned with products of this kind for applications in which the demands are especially high. A representative example is prefilled ampoules for medicals or medical applications on which are placed severe demands quite generally for integrity, sealing, sterility, purity, amounts, rigidity etc. The ampoules can be plain breakable ampoules, sealed vials etc. More elaborate ampoule types further push the demands. Syringe type ampoules for example add considerations to piston friction and sealing and restrict front end sealing options. Dual or multi chamber type ampoules additionally require openable sealings between chambers and arrangements for mixing or reliable sequential delivery. Although the present invention have a more general utility it will mainly be described in terms of these demanding applications.
Each product quality and tolerance demand translates into corresponding manufacturing problems. Generally many components and process steps are required with intermediate controls. The components as such may be a contamination source as when glass, rubber or aluminum particles are released from ampoules, sealings and cappings respectively. Most steps have to be conducted in a pure or even sterile zone with the exception of some initial and final steps. Use of human operators in sterile environments is cumbersome and the fully mechanized alternative becomes complicated when increasing the number of steps and components involved. Bulk handling of components is simple but tend to increase problems with component damage, destruction and particle release. Individual manipulation on the other hand complicates machinery and reduces throughput. Use of cassettes or carriers for multiple components only represents a tradeoff between the extremes. When the ampoules are to contain a lyophilized compound there are further constraints on the equipment used as several steps, such as closure of the ampoules, has to be conducted within a closed freeze-drying chamber and should provide for e.g. vapor transfer and uniform heat exchange and should be compatible with the necessary temperature and pressure changes involved. Syringe type ampoules generally give limited access to the interior as the openings are mainly adapted for the pistons and needle attachments and temperature and pressure changes may displace pistons inserted. Multi-chamber ampoules further add to processing and may require turning and two-way access and the additional features, such as by-pass structures, complicate manipulation.
A typical dual-chamber syringe and a process for automated manufacture of prefilled such syringes is disclosed in Neue Verpackung, No.3, 1988, p. 50-52; Drugs Made in Germany, Vol. 30, Pag. 136-140 (1987); Pharm. Ind. 46, Nr. 10 (1984) p. 1045-1048 and Pharm. Ind. 46, Nr. 3 (1984) p. 317-318. The syringe type ampoule is a dual chamber device with a front bottle type opening for needle attachment, two pistons and an exterior type by-pass for mixing a lyophilized powder in the front chamber with a reconstitution liquid in the rear chamber. The process described includes the main steps of washing and siliconizing the syringe barrels, insertion of multiple barrels in carrier trays, sterilization, introduction of middle piston through barrel rear end, turning the trays upside down, introduction of the powder solution through the front opening, lyophilization to dry powder, closure of front opening while in the lyophilizing chamber, turning of trays, introduction of the reconstitution liquid through barrel rear end, insertion of rear piston, removal of products from trays and final control and packaging. This known process express most of the general problems outlined above. It is highly restricted to the specific product processed, e.g. by requiring a special closure system and by having the barrels resting on the exterior by-pass structure in the trays.
A general problem with prior art devices is the limited considerations to combined manufacturing and construction simplicity. The U.S. Pat. No. 5,435,076 discloses a dual chamber syringe construction with reduced demands for attachment and holding structures on the ampoule proper, still with features facilitating manufacture. In embodiments shown a central barrel is surrounded by a sleeve extending from a front opening to barrel rear end, thereby making superfluous any and all fastening structures on the barrel itself. At the opening the sleeve acts to secure a sealer in sealing position and eliminates the need for a separate capping. At the rear end a fingergrip, a plunger or a delivery mechanism can be attached to the sleeve part. In spite of barrel simplicity sealer and sleeve may, if desired, be joined into a single closure component allowing sealing in a simple axial movement, also in a lyophilizing chamber. Whenever present in the manufacturing process the sleeve also protects the central barrel and, e.g. in case of damage, confines or restricts barrel debris from spreading to other products or the plant itself. Yet there are room for improvements, especially adaptations for manufacture in highly automated processes.
Accordingly there remains a need for both ampoule constructions and ampoule filling processes and equipment better suited to meet high demands in the production of prefilled ampoules.